The Necessity and Safety of Bioidentical Sex-Steroid Restoration in Menopause

Transcription

1 The Necessity and Safety of Bioidentical Sex-Steroid Restoration in Menopause Henry Lindner, MD Hormonerestoration.com This presentation is available on the CD, handout

2 All HRT is not Alike! Menopause is a hormone-deficiency state with known deleterious consequences for quality of life and health. Estradiol-progesterone-testosterone (EPT) replacement for menopause is medically necessary. Estradiol replacement is safe when transdermal and accompanied by sufficient progesterone and testosterone. Bioidentical EPT therapy does not have the cardiovascular or breast cancer risks seen with PremPro. How to provide EPT therapy to menopausal women

3 Not Just Sex Hormones Estradiol, progesterone, and testosterone are required for the growth, function and maintenance of all tissues in both sexes! Maintain brain function and health vital neurosteroids Maintain tissue health/strength: skin, hair, bone, muscle, heart Improve insulin sensitivity: belly fat, risk of diabetes Reduce blood pressure: improve endothelial function Prevent atherosclerosis: reduce risk of MI, stroke What about the loss of hormones with aging?

4 Adrenopause DHEA DHEA-S Converted into estradiol and testosterone within tissues J Clin Endocrinol Metab Aug;82(8):

5 Andropause Testosterone in Men Baltimore Longitudinal Study of Aging (BLSA). Harman et al., 2001

6 Somatopause Growth Hormone Clinical Chemistry 48, No. 12, 2002

7 Thyropause 80% decline HP response to low T4 ( g/dl) B-19yrs 20-39yrs 40-59yrs 60-79yrs 80-99yrs Endocr Rev Dec;16(6): TSH Carle, Thyroid Feb;17(2):139-44

8 pg/ml Men Menopause Testosterone Estradiol pg/ml Women Progesterone average Estradiol 0-20 pg/ml Young Old Young Old T P E

9 Hormone Loss with Age Common Assumption: Hormone loss with age is adaptive.youthful hormone levels would cause heart attacks and cancer later in life; But: Heart attacks, osteoporosis and sex-organ cancers occur years after hormones decline and in persons with lower hormone levels. Truth: Aging is not adaptive: it is pre-programmed Dying to remove individuals from the gene pool and permit evolution. Hormone loss is caused by and contributes to aging. The loss of hormones with age is both natural and deleterious.

10 Menopause is Endocrine Gland Failure The ovaries produce estradiol, progesterone and testosterone. Gradual loss of egg follicles with aging. The only endocrine glands that fail completely in all persons FSH remains high for life the brain doesn t consider menopause to be normal or good! The menopausal endocrinopathy is both natural and deleterious.

11 Estradiol Deficiency Hot flashes, night sweats Insomnia, depression, fatigue, aches Mental deterioration: poor memory recall, d risk of dementia Urogenital atrophy: vaginal dryness, incontinence Atrophy of bone, skin, and connective tissue Endothelial dysfunction, blood pressure Atherosclerosis, heart disease Insulin resistance The symptoms of menopause are warning signs of physical and mental deterioration.

12 Progesterone Deficiency Progesterone counteracts estradiol in the breasts and uterus Reduced luteal progesterone production beginning as early as age 30 luteal phase insufficiency = estrogen dominance Estrogen dominance heavy menses, breast tenderness, d risk of breast and uterine cancers. The treatment for perimenopausal estrogen dominance is lots of progesterone, not hysterectomy

13 Testosterone Deficiency Female testosterone levels are 1/10 th those of men Female testosterone drops 50% between age 20 and 40. Zumoff B, J Clin Endocrinol Metab Apr;80(4): % of serum testosterone in females comes from DHEAS. Oral estradiol HRT total testosterone 42%, DHEAS 23% Casson PR, Obstet Gynecol.1997 Dec;90(6):995-8 Birth control pills free testosterone 60%, DHEAS 30% White T, Am J Obstet Gynecol Jun;192(6):2055-9

14 Testosterone Restoration Improves energy, mood, well-being Goldstat R, Menopause Sep-Oct;10(5):390-8 Reduces fearfulness, anxiety Improves sexual desire and sensation Improves muscle strength, recovery Improves insulin sensitivity Miller KK, J Clin Endocrinol Metab Jul;92(7): With estradiol, greater in bone density Davis SR, Maturitas 1995; 21: Miller BE, Menopause Sep-Oct;7(5): Improves flow-mediated arterial dilation May decrease risk of heart attack Rako S, J Womens Health Sep;7(7):825-9 Kaczmarek A, Int J Cardiol Jan;87(1):53-7

15 Women Killers and Hormones Breast cancer, cardiovascular disease (CVD), and osteoporosis are all rare before menopause. All three diseases are related to aging and to sex-steroid deficiencies or imbalances. The youthful estradiol-progesterone-testosterone hormonal milieu protects women from these diseases.

16 Reproduction and Sex-Organ Cancers The complex female endocrine system is an evolutionary compromise; to produce and feed babies. Reproduction has costs: poses threats to female health and quality of life. Breast, uterine and ovarian tissues undergo a monthly cycle of proliferation, differentiation, and breakdown Defects in this cycle can lead to cancers in female organs and to many medical disorders.

17 Menstrual Cycle from

18 Historical Perspective Throughout history, women were usually pregnant or breast feeding; both protective against breast cancer. They had only 4 years of cycling on average. Today, women may experience 35 years of cycling d risk of breast, ovarian and uterine cancers and other diseases and disorders (PCOS, PMS, endometriosis, ovarian cysts, etc.).

19 Estradiol and Cancer Cancers are caused by genetic mutations; not sex hormones Estradiol stimulates cellular proliferation in the breasts and uterus. Unopposed estradiol and some progestins facilitate cancer initiation and growth, thereby increasing tumor detection in short-term studies.

20 Estradiol-Progesterone Complementarity Estradiol promotes proliferation in uterus and breasts. Progesterone stops proliferation and promotes maturation and differentiation in the uterus and breasts. Progesterone withdrawal sloughing and necrosis of uterine lining and breast duct epithelium. Longacre TA, Am J Surg Pathol Jun;10(6): A high persistent progesterone/estradiol ratio suppresses proliferation and prevents uterine and breast cancers.

21 Progesterone s Anti-Estrogenic Actions in Uterus and Breast Decreases synthesis of estradiol receptors Increases conversion of estradiol to inactive estrone by inducing 17β-hydroxysteroid dehydrogenase 2 Reduces conversion of inactive estrone to estradiol by inhibiting 17β-hydroxysteroid dehydrogenase 1 Increases sulfation (inactivation) of estrogens Inhibits binding of estradiol to receptors Inhibits production of estradiol by aromatization

22 Progesterone vs. Breast Cancer Premenopausal women with low progesterone levels have 5x risk of early breast cancer Cowan LD, Am J Epidem 1981;114: Breast cancer victims have progesterone resistance. Simpson HW, Br J Obstet Gynaecol Mar;105(3): BRCA1 and 2 carriers have progesterone resistance. Ma Y et al. Mol Endocrinol Jan;20(1):14-34 Guo YX et al. Nan Fang Yi Ke Da Xue Xue Bao Jul;28(7): Progesterone receptor positivity predicts better long-term survival with breast cancer Costa SD, Eur J Cancer Jul;38(10): Lamy PJ, Breast Cancer Res Treat Nov;76(1):65-71

23 Higher Luteal Progesterone Prevents Breast Cancer 6,000 women 5 yr. F/U Micheli A, Ordet Study: Int. J. Cancer 112 (2004) (2), pp See also: Sturgeon SR Cancer Causes Control Feb;15(1):45-53.

24 Progesterone vs. Breast Cancer Progesterone cream applied to the breasts reduces proliferation. Chang KJ, Fertil Steril 1995; 63: Barrat J, J Gynecol Obstet Biol Reprod (Paris). 1990;19(3): Breast cells proliferate with E2 treatment, but become quiescent when P is added. Malet C, J Steroid Biochem Mol Biol Jun;73(3-4): Foidart JM, Fertil Steril.1998 May;69(5):963-9 Estradiol promotes cancers in breast cell cultures unless progesterone is present. Russo J, J Steroid Biochem Mol Biol Oct;87(1):1-25 Estradiol upregulates cancer-promoter gene bcl-2, progesterone downregulates it. Formby B, Ann Clin Lab Sci Nov-Dec;28(6):360-9 Progesterone decreases proliferation and induces apoptosis in breast cancer cell lines. Ansquer Y, Anticancer Res Jan-Feb;25(1A):243-8 Groshong SD, Mol Endocrinol Oct;11(11):

25 EP Studies: No in Breast Cancer TD-E2=transdermal estradiol; progesterone=100mg oral capsule E3N-EPIC Cohort study 55,000 women 8 year F/U Int J Cancer Apr 10;114(3): De Lignieres B, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric 2002;5: Cordina-Duverger E, Truong T, Anger A, Sanchez M, et al. Risk of breast cancer by type of menopausal hormone therapy: a casecontrol study among post-menopausal women in France. PLoS One Nov 1;8(11):e Espié M, Daures JP, Chevallier T, Mares P, Micheletti MC, De Reilhac P. Breast cancer incidence and hormone replacement therapy: results from the MISSION study, prospective phase. Gynecol Endocrinol Jul;23(7):391-7.

26 The Europeans Get It The balance of the in vivo evidence is that progesterone does not have a cancer-promoting effect on breast tissue. Campagnoli C. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. J Steroid Biochem Mol Biol Jul;96(2): The hypothesis of progesterone decreasing the proliferative effect of estradiol in the postmenopausal breast remains highly plausible and (progesterone) should be the first choice for symptomatic postmenopausal women. Modena MG, Sismondi P, Mueck AO, Kuttenn F, Lignieres B, Verhaeghe J, Foidart JM, Caufriez A, Genazzani AR; The TREAT. Maturitas Sep 16;52(1):1-10.

27 Breast Cancer Rate vs. Age Loss of progesterone higher risk of breast cancer Ovarian function Menopause No progesterone National Cancer Institute. SEER cancer statistics review Table IV-3.

28 The Key: Intramammary Steroids Breasts produce estradiol locally from adrenal androgens (DHEA, androstenedione) Compared to the premenopausal breast, postmenopausal breast nipple aspirate fluid has: Same estradiol concentration (~youthful serum conc.) Much lower progesterone concentration Chatterton RT Clin Endocrinol Metab Mar;90(3): Breasts get progesterone from the blood, concentrate it by 3-4x. Gann PH, Cancer Epidemiol Biomarkers Prev Jan;15(1):39-44 No progesterone intramammary estrogen dominance breast cancer.

29 Testosterone Prevents Breast Cancer in Estradiol-Replete Women Testosterone opposes estradiol-induced breast stimulation. Dimitrakakis C, Menopause Jul-Aug;10(4):292-8 Somboonporn W, Endocr Rev Jun;25(3): Zhou J, FASEB J Sep;14(12): Testosterone and DHT inhibit in vitro growth of breast cancer cells. Ortmann J, Gynecol Endocrinol 2002; 16: Addition of testosterone to estrogen/progestin therapy reduces breast cancer incidence to baseline. Dimitrakakis C, Menopause Sep-Oct;11(5):531-5 (508 women; 8 yrs.) Testosterone in F M transsexuals involution of breast tissue Slagter MH, Gooren LJ, Scorilas A, Petraki CD, Diamandis EP. Effects of long-term androgen administration on breast tissue of female-to-male transsexuals. J Histochem Cytochem Aug;54(8): Testosterone is an effective treatment for breast cancer. Labrie F, Cancer Detect Prev. 1992;16(1):31-8 (review)

30 Confusion about Androgens Some studies show increased breast cancer and cardiovascular disease in premenopausal women with higher testosterone levels. Confounder PCOS: Higher premenopausal testosterone levels are caused by polycystic ovarian syndrome with high insulin and low progesterone levels. Postmenopause: DHEA and testosterone can be converted into estradiol within the breasts, at some levels may increase risk of breast cancer in the absence of progesterone.

31 Don t estrogen and progesterone cause heart attacks?

32 Coronary Heart Disease vs. Age Ovarian Function Menopause Female Risk AIHW Heart, stroke and vascular diseases - Australian facts 2004.

33 CAD and Female Hormones After menopause, women s rate of CAD rises faster than men s! Higher risk than men after 65, and higher mortality after 70! Surgical menopause mortality, atherosclerosis, 2-7x risk of heart attacks; earlier age at surgery greater risk Colditz GA, Engl J Med 1987 Apr 30;316(18): Rosenberg L, Am J Obstet Gynecol Jan;139(1):47-51 Bulk of Evidence: The youthful estradiol-progesterone-testosterone milieu is protective against CAD.

34 Estradiol vs. Cardiovascular Disease Prevents the oxidation of LDL Improves lipid profile Reduces plaque formation Reduces lipoprotein (a) Improves endothelial function Dilates arteries, reduces blood pressure Improves insulin sensitivity

35 Transdermal Estradiol Replacement Prevents Heart Attacks Løkkegaard E,. Hormone therapy and risk of myocardial infarction: a national register study. Eur Heart J Nov;29(21):

36 Oral ERT Prevents Atherosclerosis Long-term Premarin shown to reduce risk of heart disease in 40 observational and case-control studies Angiographic studies: atherosclerosis d 50-80% Estrogen reduces plaque size and progression with age. Christian RC, J Clin Endocrinol Metab Mar;87(3): EPAT trial showed less increase in carotid intimal thickness with oral estradiol vs. placebo. Hodis HN, Ann Intern Med Dec 4;135(11): Confounder: There s a problem with oral estrogens.

37 30 Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7 th Ed.

38 Osteoporosis Impact Bone loss occurs in menstruating women with lower estradiol and testosterone levels. Steinberg KK, J Clin Endocrinol Metab 1989 Sep;69(3):533-9 Menopause: 5% bone loss/year for first 5 years = 25% due to loss of estradiol! 20 yrs. post menopause 50% reduction in trabecular bone, 30% reduction in cortical bone 50% of women >65 yrs. old have spinal compression fractures 30% lifetime risk of hip fracture for 80 yr. old woman Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7 th Ed.

39 Osteoporosis A hormone deficiency disease the proper prevention and treatment is hormone restoration. Estradiol prevents resorption of old bone while testosterone and progesterone build new bone. Raisz LG, J Clin Endo Metab. 1996; 81:37-43 Barrett-Connor E, J Reprod Med Dec;44(12): EPT therapy increases both bone mineral density and collagen content, maintains normal bone remodeling Bisphosphonate drugs poison osteoclasts, suppress bone turnover rotting jaw, poor diaphyseal fracture healing and non-traumatic femur/pelvic fractures after 8 years Vits. D3 (a hormone) and K 2 preserve bone mass Iwamoto J, Keio J Med Sep;52(3):147-50

40 Estrogen Replacement Prevents Alzheimer s Disease Female: No estrogen use Longer duration of estrogen use 4x risk Male 72% used Premarin only Zandi PP, et al., Cache County Study. JAMA Nov 6;288(17): RR 0.46 in Kawas C, The Baltimore Longitudinal Study of Aging. Neurology 1997;48: RR 0.65 Paganini-Hill A, Arch Intern Med 1996;156: RR 0.4, Tang M-X, Lancet 1996;348:

41 Bioidentical Hormone Restoration is the Best Medical Practice Youthful-Optimal hormone levels and balance improve health and quality of life Logical: If a hormone is missing, replace it! If insufficient, optimize it! Use bioidentical molecules = correct chemical structure; if not bioidentical, not a human hormone! Bioidentical HRT: insulin, levothyroxine, growth hormone, cortisol (hydrocortisone), etc. Also optimize vitanutrients: Vit.D: 40-60ng/ml, ferritin: 60-80pg/ml, Omega-3 fatty acids, etc.

42 Bioidentical Hormones are not Drugs Vital parts of our neuro-endocrine-immune system Proper fit in all receptors, normal metabolism-elimination Non-toxic, inherently safe No allergic or idiosyncratic reactions No side effects, only effects! Can monitor therapy with the usual blood tests The only problems that can occur with bioidentical hormones: Excessive or insufficient dose Lack of balance with other hormones Unphysiological delivery: route, timing, etc. Exacerbation of some underlying disease

43 Q: Why does everyone think that HRT for menopause is dangerous? A: Pharmaceutical Hormone Substitution

44 Human Steroid Hormones Testosterone Estradiol DHEA Progesterone Cortisol

45 Pharmaceutical Hormone Replacement Pregnant mare s urine (Premarin ) approved in 1942 Progesterone: first steroid synthesized from a plant molecule in Poorly absorbed orally Orally-effective progestins produced norethindrone in 1952, medroxyprogesterone acetate in For 70 years HRT has meant the use of non-human steroid molecules with hormone-like effects. Human hormones cannot be patented, limited profitability

46 HRT =Hormone Substitution Therapy Progesterone substitutes: medroxyprogesterone acetate (MPA- Provera ) and 30+ other progestins Estradiol substitutes: CEE-Premarin, ethinyl estradiol Testosterone substitute: methyltestosterone in Estratest (metabolizes to super-potent estrogen, d breast cancer) Widespread confusion due to careless nomenclature: HRT, hormone, estrogen, progesterone and testosterone often refer to hormone substitutes. Substitutes are Drugs not hormones; but all problems caused by substitutes are attributed to hormones as drug class effects.

47 Oral Contraceptives Estradiol Ethinyl Estradiol Acetylene Hormone Drug EE is much more thrombogenic than oral estradiol. EE cannot be inactivated by normal oxidation. EE does not interact with estrogen receptor. EE is 12,000-60,000 times more potent by weight.

48 Premarin Conjugated Equine Estrogens Human Horse Horse Estrone Equilin Equilenin CEE contains at least 10 estrogens, only 3 are human; also contains horse androgens and progestins. Klein R The Composition of Premarin Int J Fertil 43:223

49 2002 WHI Study Premarin Arm Adverse CV effects in the first year (strokes, blood clots) Long-term reduction in CHD (anti-atherosclerotic effect). Reduced CHD and mortality when started in 50-59yr. olds, but increased when started in 70-79yr olds (established atherosclerosis). Hip fractures reduced by 39%

50 Oral Estrogens Promote Thrombosis First-pass effect on the liver clotting factors blood clots, strokes, heart attacks especially in the first year, especially in persons with coagulation disorders. Transdermal estradiol does not promote thrombosis! Oral but not transdermal estrogen is associated with an increased VTE risk. Canonico M, ESTHER study. Circulation Feb 20;115(7):840-5 Transdermal estradiol improves insulin sensitivity more than oral estrogens. Transdermal estradiol delivery mimics natural secretion.

51 CV Risk Factors: Oral Transdermal E estradiol Kuhl, Climacteric 2005;8(Suppl 1)

52 WHI Study Prempro Arm Adding Provera to Premarin caused additional heart attacks, strokes, breast cancer, and dementia (prob. vascular). Thousands of lawsuits pending drug companies running legalprotection propaganda campaign Women are told, All HRT is dangerous! Negative results of WHI have never been documented with transdermal estradiol with progesterone

53 Progesterone vs. Provera Progesterone Medroxyprogesterone acetate Hormone Drug Prempro increases cellular proliferation and breast density and affects 2500 genes; estradiol plus progesterone does not increase proliferation or density and affects only 600 genes. Murkes D, et al. Gynecol Endocrinol Oct;28 Suppl 2:12-5.

54 Scientific studies show that: Provera Progesterone Birth defects Depression Insomnia, irritability Reduces neuroprotection Fluid retention Glucocorticoid effects Raises blood sugar Vasoconstriction Smooth musc.proliferation Increases blood clotting Worsens lipid profile Causes heart attacks Increases MMP activity Increases estrogenic stimulation of breasts Promotes breast cancer Hormone of Pregnancy Improves mood Improves sleep Neuroprotective Diuretic Anti-glucocorticoid Lowers blood sugar Coronary vasodilation Decreases SM proliferation No increase in clotting Improves lipid profile No evidence of CVD Reduces MMP activity Reduces estrogenic stimulation of breasts Prevents breast cancer

55 Progestins Progesterone Drospirenone (Yasmin ) Norethisterone Levonorgestrel Acetylene Acetylene Most progestins increase breast cancer risk (RR~1.4 to 2.0) Million Women Study. Lancet Aug 9;362(9382):419-27

56 Progestin Zoo Progesterone Kuhl, Climacteric 2005;8(Suppl 1) Each progestin has a different spectrum of androgenic, estrogenic, glucocorticoid, and progestational effects.

57 Atherosclerosis and Clotting In both peripheral and cerebral vasculature (of live animals), synthetic progestins caused endothelial disruption, accumulation of monocytes in the vessel wall, platelet activation and clot formation, which are early events in atherosclerosis, inflammation and thrombosis. Natural progesterone or estrogens did not show such toxicity. Thomas T, Progestins initiate adverse events of menopausal estrogen therapy. Climacteric Dec;6(4): In addition, our data suggest that norpregnane derivatives (progestins) may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. Canonico M, ESTHER study. Circulation Feb 20;115(7):840-5

58 Any Questions about EPT benefits and safety or dangers of pharmaceutical HST? Next: How to do bioidentical EPT restoration

59 Principles of Bioidentical EPT Therapy Clinical Endocrinology: Adjust doses by symptoms first, serum levels second. Eliminate symptoms/signs of deficiency while producing no symptoms/signs of excess No side effects: all problems that occur are due to doses, balance, route or some other hormonal or medical issue. For peace of mind: Have patient sign a consent form. Provide written instructions for using hormones, preventing transfer, adjusting doses (see handouts).

60 Serum Testing Pre-treatment: order estradiol, total and free testosterone, progesterone levels rarely helpful Good to get baseline levels even in menopause. Free serum level best represents bioavailable hormone Cannot use saliva testing to monitor EPT therapy overeacts to transdermal steroid hormones spuriously high results To monitor replacement: have blood drawn ~12 hrs after daily dose for best estimate of 24hr average. Typically: AM test after bedtime application of all hormones.

61 FDA-Approved Bioidenticals Estradiol patch (Climara, Vivelle, etc.) Estradiol gel (Estrogel, Divigel, etc.) Estradiol vaginal ring (Femring ) Progesterone capsules (Prometrium, generic) Progesterone vaginal gel (Crinone ) No FDA-approved testosterone product for women Problems: weak, inconvenient, and/or expensive

62 FDA-Approved EP Replacement Estradiol patches or gels adjust dose by symptoms first, then serum levels mid-way-between-doses Symptom relief may require higher estradiol doses/strengths Oral progesterone is inefficient: immunoassay progesterone levels are 80% metabolites 200mg oral Prometrium yields same 24hr whole blood LC/MS/MS progesterone levels as 80mg progesterone in transdermal cream. Hermann AC et al., J Clin Pharmacol 2005;45: Oral progesterone metabolites are sedating AM sedation Prometrium 100 to 200mg nightly, 200mg best if tolerated Prometrium 100mg is very effective vaginally

63 Compounded Bioidentical Hormones Locally made from USP-certified micronized hormone powders Standardized compounding practices with PCCA (Professional Compounding Centers of America). Completely customizable delivery systems and concentrations Can make testosterone cream, progesterone cream, EPT combo cream and sublingual tablets (No FDA-approved equivalents) Inexpensive Often less than co-pays for FDA-approved bios. Physician-monitored: adjust dose by clinical effects and serum levels

64

65 Estradiol Restoration 3mg/0.5ml cream, 0.1ml (1 line) applied to face or neck at bedtime, as needed to 0.3ml. Good for skin tone: E2 increases skin collagen, esp. locally. Clinical Dosing: eliminate hot flashes, vaginal dryness, insomnia; avoid breast fullness-tenderness, vaginal bleeding, fluid retention 12 hr. serum estradiol usually pg/ml (similar to follicular phase) No need for estriol (E3), a weak metabolite of E2. Avoid transfer to other persons or pets (See handout)

66 Progesterone Restoration 100mg sublingual tablet at bedtime, better absorbed than cream Pulse therapy: levels very high at 3-6 hrs., low-luteal at 12 hrs. 100 mg in transdermal cream, serum levels low (2-4 ng/dl). Sufficient P prevents breast tenderness, bleeding Vaginal tabs/cream/caps for unusual bleeding tendency SAFE at any dose. Too much sedation, reflux, constipation For premenopausal menorrhagia or early breakthrough bleeding try twice-daily sublingual P or vaginal P in luteal phase or continuously

67 Testosterone Restoration 2mg/0.2ml Versabase cream, apply 0.1ml (1 line) to inner labia Best absorption genitally, improves libido and vaginal moisture, no clitoromegaly reported. If not tolerated labially, use higher strength/amount to inner thighs or back of knees (no local hair growth) Lower T dose if excess acne or facial hair some pimples and body hair are the natural effect of youthful testosterone levels! Good dose: 12 hr. serum total testosterone usually high, but free testosterone mid-range (0-2.2pg/ml or pg/ml). There is more androgen effect than serum testosterone levels suggest because DHT is usually high.

68 Troubleshooting Recurrent bleeding/spotting may occur due to submucosal fibroid, polyp, or adenomyosis; try lower estradiol dose, higher progesterone dose or vaginal progesterone. Postmenopausal cancer-surveillance guidelines do not apply: Endometrial evaluation only if bleeding persists in spite of dose changes and off EP therapy. If hot flashes worsen with estradiol, lower dose then increase very slowly, try AM dosing Inability to tolerate estradiol or progesterone may be due to cortisol deficiency (a.k.a. adrenal insufficiency). Hair loss: estradiol, testosterone (some women have androgen-sensitive alopecia)

69 Women with Breast Cancer? Almost all studies of estrogen/progestin therapy in women with breast cancer show no increase in recurrence rates. One human and two rat studies indicate that bioidentical estradiol-progesterone therapy is an effective preventative and treatment for breast cancer. Estradiol-deprivation therapies (tamoxifen, aromatase inhibitors) only reduce 5-10 year recurrence rates, they do not cure cancer; and have a high cost in quality of life and health. Plotkin, D. Estradiol-progesterone replacement is not contraindicated and may reduce recurrence rates due to the anti-proliferative effects of progesterone. Women with BC have the right to HRT with informed consent.

70 For More Information See presentation, handouts, practice forms on CD Essays on Hormone Restoration Thousands of abstracts under The Evidence Contact me:

71 Q: Why don t physicians and the public know about the benefits and safety of bioidentical HRT? A: Pharmaceutical Corporation Clout

72 HRT Information Warfare After WHI report, lawsuits piled up and women switched from Prempro to pharmacy-compounded bioidentical hormones. US professional assocations proclaimed All HRT is alike ; FDAapproved and compounded bioidentical hormones had the same risks as all other FDA-approved hormone products. The North American Menopause Society (NAMS) published an antibioidentical article confounding bioidentical HRT with questions surrounding compounding and saliva testing. Boothby L, Bioidentical hormone therapy: a review,menopause 2004 Vol. 11, No. 3, pp Bioidentical ridiculed as a marketing term, fad, snake oil. Muddying the waters: NAMS advised that progesterone and progestins now be called progestogens! NAMS tells women and their doctors: Use any FDA-approved progestogen, but don t use compounded progesterone.

73 ACOG Helps Big Pharma October 31, 2005, ACOG NEWS RELEASE There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies, ACOG recommends that they should be considered to have the same safety issues as those hormone products that are approved by the FDA and may also have additional risks unique to the compounding process. Furthermore, hormone therapy does not belong to a class of drugs with an indication for individualized dosing (!?!) ALL LIES! ACOG, NAMS and The Endocrine Society are funded by Pharmaceutical Corporations. Conflict of Interest: professional associations and policy makers should have zero (0) industry funding. Rothman DJ et al, Professional medical associations and their relationships with industry: a proposal for controlling conflict of interest. JAMA Apr 1;301(13):

74 Wyeth Jumps In October 2005: Wyeth (maker of Prempro ) files citizen petition asking FDA to impose restrictions on physicians ability to prescribe and pharmacists ability to make compounded bioidentical hormones! Demands that compounding pharmacies cease promoting bioidentical hormones as more natural (??) or safer (??) than its dangerous hormone substitutes! Demands the same warnings for compounded bioidentical hormone preparations as for its dangerous hormone substitutes Motives: Legal protection (Prempro lawsuits) and market share (Prempro is still being prescribed!)

75 HRT Wars: Conclusions Women have been victimized by propaganda from pharmaceutical corporations and the professional associations that they fund. Things are changing: Recent guidelines from International Menopause Society, NAMS and The Endocrine Society contain statements about the greater safety of transdermal estradiol and progesterone. ( may not have the same risks ) Estradiol (transdermal), progesterone and testosterone restoration will soon be standard medical practice.